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Richard P Evershed - One of the best experts on this subject based on the ideXlab platform.
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situ polar organic chemical integrative sampling (POCIS) of steroidal Estrogens in sewage treatment works discharge and river
2020Co-Authors: Thitima Rujiralai, Ian D Bull, Neville Llewellyn, Richard P EvershedAbstract:A passive sampler (the polar organic chemical integrative sampler; POCIS) was assessed for its ability to sample natural Estrogens (17b-estradiol, E2; estrone, E1 and estriol, E3) and the synthetic Estrogen (17a-ethynylestradiol, EE2) in the outlet of a sewage treatment works over several weeks. The performance of the POCIS was investigated and optimised in the laboratory before field deployment with high recoveries (66-99%) were achieved for all Estrogens. Moreover, it was shown that POCIS does not exhibit any preferential selectivity towards any of the target compounds. The sampling rates of E1, E2 and E3 were 0.018 AE 0.009, 0.025 AE 0.014 and 0.033 AE 0.019 L d À1 , respectively. Following field deployments of 28 days in the discharge of a sewage works, POCIS was shown to enhance the sensitivity of Estrogen detection, especially for E3, and provide time-weighted average (TWA) concentrations of E1, E2 and E3, ranging from undetectable to 12 ng L À1 upstream of the outflow of a sewage treatment works, 13 to 91 ng L À1 at the outflow and 8 to 39 ng L À1 downstream of the outflow. This revealed that E1, E2 and E3 are not completely removed during sewage treatment, with concentrations most likely being maintained by contributions from Conjugated Estrogen analogues. Grab water samples showed considerable variation in the concentrations of Estrogens over a longer period (6 months). The results confirm that POCIS is an effective and non-discriminatory method for the detection of low concentrations of Estrogens in the aquatic environment
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in situ polar organic chemical integrative sampling pocis of steroidal Estrogens in sewage treatment works discharge and river water
Journal of Environmental Monitoring, 2011Co-Authors: Thitima Rujiralai, Ian D Bull, Neville R Llewellyn, Richard P EvershedAbstract:A passive sampler (the polar organic chemical integrative sampler; POCIS) was assessed for its ability to sample natural Estrogens (17β-estradiol, E2; estrone, E1 and estriol, E3) and the synthetic Estrogen (17α-ethynylestradiol, EE2) in the outlet of a sewage treatment works over several weeks. The performance of the POCIS was investigated and optimised in the laboratory before field deployment with high recoveries (66–99%) were achieved for all Estrogens. Moreover, it was shown that POCIS does not exhibit any preferential selectivity towards any of the target compounds. The sampling rates of E1, E2 and E3 were 0.018 ± 0.009, 0.025 ± 0.014 and 0.033 ± 0.019 L d−1, respectively. Following field deployments of 28 days in the discharge of a sewage works, POCIS was shown to enhance the sensitivity of Estrogen detection, especially for E3, and provide time-weighted average (TWA) concentrations of E1, E2 and E3, ranging from undetectable to 12 ng L−1upstream of the outflow of a sewage treatment works, 13 to 91 ng L−1 at the outflow and 8 to 39 ng L−1downstream of the outflow. This revealed that E1, E2 and E3 are not completely removed during sewage treatment, with concentrations most likely being maintained by contributions from Conjugated Estrogen analogues. Grab water samples showed considerable variation in the concentrations of Estrogens over a longer period (6 months). The results confirm that POCIS is an effective and non-discriminatory method for the detection of low concentrations of Estrogens in the aquatic environment.
James H Pickar - One of the best experts on this subject based on the ideXlab platform.
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Conjugated Estrogen bazedoxifene tablets for the treatment of moderate to severe vasomotor symptoms associated with menopause
Women's Health, 2014Co-Authors: Sebastian Mirkin, Barry S Komm, James H PickarAbstract:Conjugated Estrogen/bazedoxifene (CE/BZA) therapy represents a new, progestin-free treatment in the management of postmenopausal health. CE/BZA pairs CE with the selective Estrogen receptor modulator, BZA. The rationale for the development of CE/BZA was that BZA, acting primarily as a selective Estrogen receptor degrader in uterine and breast tissue, would sufficiently inhibit the proliferative effects of CE on the endometrium. The absence of a progestin would reduce the incidence of uterine bleeding, breast pain and increased breast density associated with progestin-containing hormone therapy. CE/BZA has been evaluated in five multicenter, randomized, double-blind, placebo-controlled, and active-controlled Phase III trials known as the SMART trials. CE/BZA has been shown to maintain the established benefits of Estrogen therapy for treatment of vasomotor symptoms and prevention of a loss in bone mineral density (bone mass), while minimizing certain Estrogenic effects, particularly in the uterine endometrium and breast.
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management of osteoporosis and menopausal symptoms focus on bazedoxifene Conjugated Estrogen combination
International Journal of Women's Health, 2013Co-Authors: Sebastian Mirkin, James H PickarAbstract:Loss of Estrogen production in women during menopause results in a state of Estrogen deficiency which has been associated with multiple problems, including vasomotor symptoms, symptoms of vulvovaginal atrophy, bone loss, and difficulties with sleep, mood, memory, and sexual activity. The only treatment option currently available to address multiple postmenopausal symptoms in women with an intact uterus is Estrogen/progestin-containing hormone therapy (HT). Concerns surrounding side effects and published data regarding the association of HT with the increased risk for breast cancer have induced a decrease in the number of women seeking, initiating, and continuing this type of therapy. A combination containing bazedoxifene and Conjugated Estrogens (BZA/CE) maintains the established benefits of Estrogen therapy for treatment of postmenopausal vasomotor symptoms, vulvovaginal atrophy, and osteoporosis, while certain Estrogenic effects, such as stimulation of the uterus and breast, are antagonized without the side effects associated with HT. BZA/CE has been evaluated in a series of multicenter, randomized, double-blind, placebo-controlled, and active-controlled Phase III trials known as the Selective Estrogens, Menopause, And Response to Therapy (SMART) trials. BZA/CE demonstrated clinically meaningful improvements in vasomotor symptoms, vulvovaginal atrophy, and a protective effect on the skeleton. These clinical benefits were associated with an acceptable safety profile and an improved tolerability compared with HT. BZA/CE showed a favorable safety profile on the breast, endometrium, and ovaries. The incidence of venous thromboembolism was low and the risk does not appear to be any greater than for CE alone or BZA alone or greater than HT. The incidence of coronary heart disease and cerebrovascular accidents were similar to placebo. The overall incidence of cancer (including breast cancer) was low and similar to placebo. The SMART trials demonstrate that BZA/CE is an alternative option for treating non-hysterectomized, symptomatic, postmenopausal women.
Joann E. Manson - One of the best experts on this subject based on the ideXlab platform.
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Use of Oral Conjugated Estrogen Alone and Risk of Breast Cancer
American journal of epidemiology, 2006Co-Authors: Shumin M. Zhang, Joann E. Manson, Kathryn M. Rexrode, Nancy R. Cook, Julie E. Buring, I-min LeeAbstract:The authors conducted a prospective cohort analysis in the Women's Health Study (1992-2004), a completed randomized trial assessing aspirin and vitamin E in the primary prevention of cancer and cardiovascular disease, to evaluate use of oral Conjugated Estrogen alone (0.625 mg/day) and breast cancer risk in a time-varying fashion. Over an average of 10 years of follow-up, 305 incident cases of breast cancer (258 invasive and 47 in situ cancers) were documented among 12,718 women aged 45 years or more who were either consistent current users of oral Conjugated Estrogen alone (0.625 mg/day) or never users of any type of postmenopausal hormones at baseline and during follow-up. The multivariable hazard ratios comparing "consistent current users" with "never users" were 1.11 (95% confidence interval: 0.79, 1.56) for total breast cancer and 1.13 (95% confidence interval: 0.77, 1.64) for invasive cases. No significant associations were observed for use of less than 8 and 8 years or more. Restricting the analyses to women with prior hysterectomy somewhat strengthened the associations, albeit still not significantly. These data, like those from the Women's Health Initiative, show no significant increase in breast cancer risk with use of oral Conjugated Estrogen alone (0.625 mg/day), but a small increase or decrease in risk cannot be excluded.
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a prospective observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease
Annals of Internal Medicine, 2000Co-Authors: Francine Grodstein, Joann E. Manson, Graham A Colditz, Walter C Willett, Frank E Speizer, Meir J StampferAbstract:Postmenopausal hormone use appears to decrease risk for major coronary events in women without previous heart disease. Furthermore, 0.3 mg of oral Conjugated Estrogen daily is associated with a red...
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a prospective observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease
Annals of Internal Medicine, 2000Co-Authors: Francine Grodstein, Joann E. Manson, Graham A Colditz, Walter C Willett, Frank E Speizer, Meir J StampferAbstract:BACKGROUND: Most primary prevention studies have found that long-term users of postmenopausal hormone therapy are at lower risk for coronary events, but numerous questions remain. An adverse influence of hormone therapy on cardiovascular risk has been suggested during the initial year of use; however, few data are available on short-term hormone therapy. In addition, the cardiovascular effects of daily doses of oral Conjugated Estrogen lower than 0.625 mg are unknown, and few studies have examined Estrogen plus progestin in this regard. OBJECTIVE: To investigate duration, dose, and type of postmenopausal hormone therapy and primary prevention of cardiovascular disease. DESIGN: Prospective, observational cohort study. SETTING: Nurses' Health Study, with follow-up from 1976 to 1996. PATIENTS: 70 533 postmenopausal women, in whom 1258 major coronary events (nonfatal myocardial infarction or fatal coronary disease) and 767 strokes were identified. MEASUREMENTS: Details of postmenopausal hormone use were ascertained by using biennial questionnaires. Cardiovascular disease was established by using a questionnaire and was confirmed by medical record review. Logistic regression models were used to calculate relative risks and 95% CIs, adjusted for confounders. RESULTS: When all cardiovascular risk factors were considered, the risk for major coronary events was lower among current users of hormone therapy, including short-term users, compared with never-users (relative risk, 0.61 [95% CI, 0.52 to 0.71]). Among women taking oral Conjugated Estrogen, the risk for coronary events was similarly reduced in those currently taking 0.625 mg daily (relative risk, 0.54 [CI, 0.44 to 0.67]) and those taking 0.3 mg daily (relative risk, 0.58 [CI, 0. 37 to 0.92]) compared with never-users. However, the risk for stroke was statistically significantly increased among women taking 0.625 mg or more of oral Conjugated Estrogen daily (relative risk, 1.35 [CI, 1.08 to 1.68] for 0.625 mg/d and 1.63 [CI, 1.18 to 2.26] for >/=1.25 mg/d) and those taking Estrogen plus progestin (relative risk, 1.45 [CI, 1.10 to 1.92]). Overall, little relation was observed between combination hormone therapy and risk for cardiovascular disease (major coronary heart disease plus stroke) (relative risk, 0.91 [CI, 0.75 to 1.11]). CONCLUSIONS: Postmenopausal hormone use appears to decrease risk for major coronary events in women without previous heart disease. Furthermore, 0.3 mg of oral Conjugated Estrogen daily is associated with a reduction similar to that seen with the standard dose of 0.625 mg. However, Estrogen at daily doses of 0.625 mg or greater and in combination with progestin may increase risk for stroke.
David M. Herrington - One of the best experts on this subject based on the ideXlab platform.
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effects of Estrogen replacement on the progression of coronary artery atherosclerosis
The New England Journal of Medicine, 2000Co-Authors: David M. Herrington, David M Reboussin, K B Brosnihan, Penny C Sharp, Sally A Shumaker, Thomas E Snyder, Curt D Furberg, Glen J Kowalchuk, Thomas D Stuckey, William J RogersAbstract:Background Heart disease is a major cause of illness and death in women. To understand better the role of Estrogen in the treatment and prevention of heart disease, more information is needed about its effects on coronary atherosclerosis and the extent to which concomitant progestin therapy may modify these effects. Methods We randomly assigned a total of 309 women with angiographically verified coronary disease to receive 0.625 mg of Conjugated Estrogen per day, 0.625 mg of Conjugated Estrogen plus 2.5 mg of medroxyprogesterone acetate per day, or placebo. The women were followed for a mean (±SD) of 3.2±0.6 years. Base-line and follow-up coronary angiograms were analyzed by quantitative methods. Results Estrogen and Estrogen plus medroxyprogesterone acetate produced significant reductions in low-density lipoprotein cholesterol levels (9.4 percent and 16.5 percent, respectively) and significant increases in high-density lipoprotein cholesterol levels (18.8 percent and 14.2 percent, respectively); however,...
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effects of Estrogen replacement on the progression of coronary artery atherosclerosis
The New England Journal of Medicine, 2000Co-Authors: David M. Herrington, David M Reboussin, K B Brosnihan, Penny C Sharp, Sally A Shumaker, Thomas E Snyder, Curt D Furberg, Glen J Kowalchuk, Thomas D Stuckey, William J RogersAbstract:BACKGROUND: Heart disease is a major cause of illness and death in women. To understand better the role of Estrogen in the treatment and prevention of heart disease, more information is needed about its effects on coronary atherosclerosis and the extent to which concomitant progestin therapy may modify these effects. METHODS: We randomly assigned a total of 309 women with angiographically verified coronary disease to receive 0.625 mg of Conjugated Estrogen per day, 0.625 mg of Conjugated Estrogen plus 2.5 mg of medroxyprogesterone acetate per day, or placebo. The women were followed for a mean (+/-SD) of 3.2+/-0.6 years. Base-line and follow-up coronary angiograms were analyzed by quantitative coronary angiography. RESULTS: Estrogen and Estrogen plus medroxyprogesterone acetate produced significant reductions in low-density lipoprotein cholesterol levels (9.4 percent and 16.5 percent, respectively) and significant increases in high-density lipoprotein cholesterol levels (18.8 percent and 14.2 percent, respectively); however, neither treatment altered the progression of coronary atherosclerosis. After adjustment for measurements at base line, the mean (+/-SE) minimal coronary-artery diameters at follow-up were 1.87+/-0.02 mm, 1.84+/-0.02 mm, and 1.87+/-0.02 mm in women assigned to Estrogen, Estrogen plus medroxyprogesterone acetate, and placebo, respectively. The differences between the values for the two active-treatment groups and the value for the placebo group were not significant. Analyses of several secondary angiographic outcomes and subgroups of women produced similar results. The rates of clinical cardiovascular events were also similar among the treatment groups. CONCLUSIONS: Neither Estrogen alone nor Estrogen plus medroxyprogesterone acetate affected the progression of coronary atherosclerosis in women with established disease. These results suggest that such women should not use Estrogen replacement with an expectation of cardiovascular benefit.
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cardiovascular effects of droloxifene a new selective Estrogen receptor modulator in healthy postmenopausal women
Arteriosclerosis Thrombosis and Vascular Biology, 2000Co-Authors: David M. Herrington, Benjamin E Pusser, Tom Thuren, Bridget K Brosnihan, Eliot A. Brinton, Ward A Riley, David B. MacleanAbstract:Abstract —Selective Estrogen receptor modulators, like tamoxifen and related compounds, have mixed Estrogen agonistic/antagonistic effects. Tamoxifen may confer significant cardiovascular benefits without the Estrogen-associated risks of endometrial and breast cancer. Droloxifene, a structural analogue of tamoxifen, has Estrogen agonistic effects on bone and antagonistic effects on endometrial and breast tissue. Its cardiovascular effects in women are unknown. We enrolled 24 healthy postmenopausal women in a randomized, double-blind, 2-period crossover trial comparing the effects of droloxifene (60 mg/d) with Conjugated Estrogen (0.625 mg/d). Plasma lipids, coagulation and fibrinolytic factors, and brachial flow-mediated vasodilator responses were measured at the beginning and end of each treatment period. Droloxifene and Estrogen resulted in 16.6% and 12.0% reductions, respectively, in low density lipoprotein cholesterol ( P <0.001) and 13.2% and 9.5% reductions, respectively, in lipoprotein(a) ( P <0.05). In contrast, Estrogen, but not droloxifene, increased high density lipoprotein (18.5%, P <0.001). Droloxifene also reduced fibrinogen by 17.8% versus a 7.3% reduction with Estrogen ( P =0.004) but produced no Estrogen-like changes in plasminogen, plasminogen activator inhibitor-1, or tissue plasminogen activator. Droloxifene and Estrogen produced 36.4% and 27.3% increases, respectively, in flow-mediated vasodilation (percent change from baseline, P <0.05 for both). Droloxifene has Estrogen agonistic properties regarding low density lipoprotein and lipoprotein(a) metabolism, certain coagulation factors, and endothelium-dependent vasodilation but, unlike Estrogen, has no effect on high density lipoprotein/triglyceride metabolism and the fibrinolytic cascade. It remains unknown whether droloxifene can confer a true cardiovascular benefit.
William J Rogers - One of the best experts on this subject based on the ideXlab platform.
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effects of Estrogen replacement on the progression of coronary artery atherosclerosis
The New England Journal of Medicine, 2000Co-Authors: David M. Herrington, David M Reboussin, K B Brosnihan, Penny C Sharp, Sally A Shumaker, Thomas E Snyder, Curt D Furberg, Glen J Kowalchuk, Thomas D Stuckey, William J RogersAbstract:BACKGROUND: Heart disease is a major cause of illness and death in women. To understand better the role of Estrogen in the treatment and prevention of heart disease, more information is needed about its effects on coronary atherosclerosis and the extent to which concomitant progestin therapy may modify these effects. METHODS: We randomly assigned a total of 309 women with angiographically verified coronary disease to receive 0.625 mg of Conjugated Estrogen per day, 0.625 mg of Conjugated Estrogen plus 2.5 mg of medroxyprogesterone acetate per day, or placebo. The women were followed for a mean (+/-SD) of 3.2+/-0.6 years. Base-line and follow-up coronary angiograms were analyzed by quantitative coronary angiography. RESULTS: Estrogen and Estrogen plus medroxyprogesterone acetate produced significant reductions in low-density lipoprotein cholesterol levels (9.4 percent and 16.5 percent, respectively) and significant increases in high-density lipoprotein cholesterol levels (18.8 percent and 14.2 percent, respectively); however, neither treatment altered the progression of coronary atherosclerosis. After adjustment for measurements at base line, the mean (+/-SE) minimal coronary-artery diameters at follow-up were 1.87+/-0.02 mm, 1.84+/-0.02 mm, and 1.87+/-0.02 mm in women assigned to Estrogen, Estrogen plus medroxyprogesterone acetate, and placebo, respectively. The differences between the values for the two active-treatment groups and the value for the placebo group were not significant. Analyses of several secondary angiographic outcomes and subgroups of women produced similar results. The rates of clinical cardiovascular events were also similar among the treatment groups. CONCLUSIONS: Neither Estrogen alone nor Estrogen plus medroxyprogesterone acetate affected the progression of coronary atherosclerosis in women with established disease. These results suggest that such women should not use Estrogen replacement with an expectation of cardiovascular benefit.
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effects of Estrogen replacement on the progression of coronary artery atherosclerosis
The New England Journal of Medicine, 2000Co-Authors: David M. Herrington, David M Reboussin, K B Brosnihan, Penny C Sharp, Sally A Shumaker, Thomas E Snyder, Curt D Furberg, Glen J Kowalchuk, Thomas D Stuckey, William J RogersAbstract:Background Heart disease is a major cause of illness and death in women. To understand better the role of Estrogen in the treatment and prevention of heart disease, more information is needed about its effects on coronary atherosclerosis and the extent to which concomitant progestin therapy may modify these effects. Methods We randomly assigned a total of 309 women with angiographically verified coronary disease to receive 0.625 mg of Conjugated Estrogen per day, 0.625 mg of Conjugated Estrogen plus 2.5 mg of medroxyprogesterone acetate per day, or placebo. The women were followed for a mean (±SD) of 3.2±0.6 years. Base-line and follow-up coronary angiograms were analyzed by quantitative methods. Results Estrogen and Estrogen plus medroxyprogesterone acetate produced significant reductions in low-density lipoprotein cholesterol levels (9.4 percent and 16.5 percent, respectively) and significant increases in high-density lipoprotein cholesterol levels (18.8 percent and 14.2 percent, respectively); however,...